The goal of the research described in this proposal is to provide basic understanding of the coupling between electrical activity and metabolism in central nervous system tissues. This will be investigated by monitoring the redox status of mitochondrial respiratory chain components (cytochrome a,a3 and NAD+/NADH), extracellular potassium ion activity, tissue oxygen tension and electrical activity in isolated cerebral tissues in vitro, where glucose and oxygen availability can be controlled precisely. These projects will determine whether oxidative metabolic rate, ion homeostasis, an neuronal function are under continuous regulation by the availability of glucose and oxygen, or whether there are "critical" thresholds of glucose and oxygen provision, below which neuronal function and metabolism are not maintained. These experiments will also determine whether the state of neuronal excitation sets the threshold for loss of function during glucose or oxygen insufficiency. In addition, it is anticipated that alterations in the redox states of mitochondrial respiratory chain components will reflect the loss of metabolic and electrophysiological function during glucose and oxygen insufficiency, and that these signals will provide a basis for defining deficiencies in metabolism and electrophysiology and in the intact brain. It is toward this long-term goal of providing means by which metabolism and electrophysiology can be evaluated in the intact brain, that this research is directed.